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Annals of Pediatric Cardiology 2024Noonan syndrome (NS) is a pleomorphic genetic disorder. Up to 50-80% of individuals have associated congenital heart disease. The scope of cardiac disease in NS is quite...
Noonan syndrome (NS) is a pleomorphic genetic disorder. Up to 50-80% of individuals have associated congenital heart disease. The scope of cardiac disease in NS is quite variable depending on the gene mutation. The most common forms of cardiac defects include pulmonary stenosis, hypertrophic cardiomyopathy (HCM), atrial septal defect and left-sided lesions. Amongst the rare vascular abnormalities few case reports have been mentioned about coronary artery lesions apart from sinus of Valsalva aneurysm, aortic dissection, intracranial aneurysm. This is a case report a rare case of asymptomatic coronary artery aneurysm in a young male with NS. There is lack of unified protocol for the screening, diagnosis, treatment, and follow-up of coronary artery disease in patients with NS. We conclude, echocardiography is sufficient in most cases in children. But a CT scan is appropriate in adults or when other lesions are suspected.
PubMed: 38933057
DOI: 10.4103/apc.apc_145_23 -
Frontiers in Molecular Neuroscience 2024The Anaphase Promoting Complex (APC/C), an E3 ubiquitin ligase, plays a key role in cell cycle control, but it is also thought to operate in postmitotic neurons. Most...
INTRODUCTION
The Anaphase Promoting Complex (APC/C), an E3 ubiquitin ligase, plays a key role in cell cycle control, but it is also thought to operate in postmitotic neurons. Most studies linking APC/C function to neuron biology employed perturbations of the APC/C activators, cell division cycle protein 20 (Cdc20) and Cdc20 homologue 1 (Cdh1). However, multiple lines of evidence indicate that Cdh1 and Cdc20 can function in APC/C-independent contexts, so that the effects of their perturbation cannot strictly be linked to APC/C function.
METHODS
We therefore deleted the gene encoding Anaphase Promoting Complex 4 (APC4), a core APC/C component, in neurons cultured from conditional knockout (cKO) mice.
RESULTS
Our data indicate that several previously published substrates are actually not APC/C substrates, whereas ubiquitin specific peptidase 1 (USP1) protein levels are altered in APC4 knockout (KO) neurons. We propose a model where the APC/C ubiquitylates USP1 early in development, but later ubiquitylates a substrate that directly or indirectly stabilizes USP1. We further discovered a novel role of the APC/C in regulating the number of neurites exiting somata, but we were unable to confirm prior data indicating that the APC/C regulates neurite length, neurite complexity, and synaptogenesis. Finally, we show that APC4 SUMOylation does not impact the ability of the APC/C to control the number of primary neurites or USP1 protein levels.
DISCUSSION
Our data indicate that perturbation studies aimed at dissecting APC/C biology must focus on core APC/C components rather than the APC/C activators, Cdh20 and Cdh1.
PubMed: 38932933
DOI: 10.3389/fnmol.2024.1352782 -
Anatomy & Cell Biology Jun 2024Anticipating a wide range of morphological variations of arterial anatomy of foregut derivatives beyond the classical pattern, a precise understanding is pertinent to...
Anticipating a wide range of morphological variations of arterial anatomy of foregut derivatives beyond the classical pattern, a precise understanding is pertinent to preoperative diagnosis, operative procedure and to avoid potentially devastating post-operative outcome during various traumatic and non-traumatic vascular insult of foregut. The study aimed to revisit the morphological details and update unusual configurations of arteries of foregut to establish clinico-anatomical correlations. This study described the detailed branching pattern of coeliac trunk (CT) as principal artery of foregut with source & course of hepatic, gastric, duodenal and pancreatic branches in 58 cadaveric dissections. Based on morphology, different types and subtypes were made. The descriptions were explained using figures and pertinent tables. Among classical branches of CT, splenic artery was found as most stable whereas other two branches were found to be most variable with missing common hepatic artery in 11 cases. In addition to classical trifurcation (65.52%), different types of bifurcation (12.07%) and tetrafurcations (22.41%) of CT were observed. Regarding variations of hepatic arteries (27.59%), both non-classical origin and accessory hepatic branches were found. In case of gastric branches, more variant origins were seen with right gastric (50%) as compared to left gastric artery (34.48%). Other morphological variations included non-classical origin of gastro-duodenal artery (18.96%) along with presence of accessory pancreatic (17.13%) and duodenal arteries (6.38%). Awareness of anatomical variations regarding circulatory dynamics of foregut is worth knowing in order to facilitate successful planning of surgery involving upper abdominal organs with least complications.
PubMed: 38932617
DOI: 10.5115/acb.24.078 -
Endocrinology, Diabetes & Metabolism Jul 2024Iatrogenic hypoparathyroidism is a common cause of postthyroidectomy hypocalcaemia. It has varying incidence rates after neck surgery in Saudi Arabia, ranging from 0.07%...
BACKGROUND
Iatrogenic hypoparathyroidism is a common cause of postthyroidectomy hypocalcaemia. It has varying incidence rates after neck surgery in Saudi Arabia, ranging from 0.07% to 65.30%. Hypoparathyroidism can manifest with a spectrum of symptoms, ranging from mild to severe and life-threatening. This study aimed to assess the rate and predictors of iatrogenic hypoparathyroidism after thyroid surgery and its natural course.
METHODS
This retrospective cohort study used a data collection form to extract patient information from the electronic healthcare system (Best-Care) for patients treated from 2017 to 2022. Patients' demographics, surgical specifics and biochemical profiles were recorded for subsequent analysis.
RESULTS
Among the 343 patients who underwent thyroidectomy, 130 (37.9%) developed hypoparathyroidism, primarily within the first day after surgery. Calcium or vitamin D supplementation before surgery did not significantly influence hypoparathyroidism development. Notably, extensive combined lymph node dissection was significantly associated with postoperative hypoparathyroidism development (p = 0.0004). More patients who underwent central and lateral lymph node dissection (n = 19, 79.17%) developed hypoparathyroidism than patients who underwent central (n = 18, 40.91%) or lateral (n = 8, 38.10%) dissection alone. Permanent hypoparathyroidism was observed in 40 patients (11.66%).
CONCLUSION
This study revealed a high incidence of iatrogenic hypoparathyroidism and high rates of permanent hypoparathyroidism. Further research is warranted to better comprehend the risk factors and optimise management strategies for iatrogenic hypoparathyroidism. Overall, our findings emphasise the need for vigilant monitoring and effective management of patients undergoing thyroidectomy and the significance of postoperative replacement therapies.
Topics: Humans; Thyroidectomy; Hypoparathyroidism; Retrospective Studies; Female; Male; Iatrogenic Disease; Middle Aged; Adult; Postoperative Complications; Hypocalcemia; Aged; Saudi Arabia; Incidence; Cohort Studies; Risk Factors
PubMed: 38932435
DOI: 10.1002/edm2.506 -
Vaccines Jun 2024T help (Th), stimulation of toll-like receptors (pathogen-associated molecular patterns, PAMPs), and antigen organization and repetitiveness (pathogen-associated...
Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response.
T help (Th), stimulation of toll-like receptors (pathogen-associated molecular patterns, PAMPs), and antigen organization and repetitiveness (pathogen-associated structural patterns, PASPs) were shown numerous times to be important in driving B-cell and antibody responses. In this study, we dissected the individual contributions of these parameters using newly developed "Immune-tag" technology. As model antigens, we used eGFP and the third domain of the dengue virus 1 envelope protein (DV1 EDIII), the major target of virus-neutralizing antibodies. The respective proteins were expressed alone or genetically fused to the N-terminal fragment of the cucumber mosaic virus (CMV) capsid protein-nCMV, rendering the antigens oligomeric. In a step-by-step manner, RNA was attached as a PAMP, and/or a universal Th-cell epitope was genetically added for additional Th. Finally, a PASP was added to the constructs by displaying the antigens highly organized and repetitively on the surface of CMV-derived virus-like particles (CuMV VLPs). Sera from immunized mice demonstrated that each component contributed stepwise to the immunogenicity of both proteins. All components combined in the CuMV VLP platform induced by far the highest antibody responses. In addition, the DV1 EDIII induced high levels of DENV-1-neutralizing antibodies only if displayed on VLPs. Thus, combining multiple cues typically associated with viruses results in optimal antibody responses.
PubMed: 38932390
DOI: 10.3390/vaccines12060661 -
Viruses Jun 2024Previous studies reported that the hepatitis C virus (HCV) could help disseminate the hepatitis D virus (HDV) in vivo through the unrelated hepatitis B virus (HBV), but...
Previous studies reported that the hepatitis C virus (HCV) could help disseminate the hepatitis D virus (HDV) in vivo through the unrelated hepatitis B virus (HBV), but with essentially inconclusive results. To try to shed light on this still-debated topic, 146 anti-HCV-positive subjects (of whom 91 HCV/HIV co-infected, and 43 with prior HCV eradication) were screened for anti-HDV antibodies (anti-HD), after careful selection for negativity to any serologic or virologic marker of current or past HBV infection. One single HCV/HIV co-infected patient (0.7%) tested highly positive for anti-HD, but with no positive HDV-RNA. Her husband, in turn, was a HCV/HIV co-infected subject with a previous contact with HBV. While conducting a thorough review of the relevant literature, the authors attempted to exhaustively describe the medical history of both the anti-HD-positive patient and her partner, believing it to be the key to dissecting the possible complex mechanisms of HDV transmission from one subject to another, and speculating that in the present case, it may have been HCV itself that behaved as an HDV helper virus. In conclusion, this preliminary research, while needing further validation in large prospective studies, provided some further evidence of a role of HCV in HDV dissemination in humans.
Topics: Humans; Hepatitis D; Hepatitis Delta Virus; Hepacivirus; Female; Hepatitis C; Coinfection; Male; Helper Viruses; Hepatitis Antibodies; Adult; Middle Aged; HIV Infections; RNA, Viral; Hepatitis B
PubMed: 38932284
DOI: 10.3390/v16060992 -
Viruses Jun 2024Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is... (Review)
Review
Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection.
Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus's direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection.
Topics: Simian Immunodeficiency Virus; Animals; HIV Infections; Simian Acquired Immunodeficiency Syndrome; Humans; HIV; Disease Models, Animal; Haplorhini; Lymphocyte Depletion
PubMed: 38932264
DOI: 10.3390/v16060972 -
Nutrients Jun 2024Branched-chain amino acids (BCAAs), comprising leucine (Leu), isoleucine (Ile), and valine (Val), are essential nutrients vital for protein synthesis and metabolic... (Review)
Review
Branched-chain amino acids (BCAAs), comprising leucine (Leu), isoleucine (Ile), and valine (Val), are essential nutrients vital for protein synthesis and metabolic regulation via specialized signaling networks. Their association with cardiovascular diseases (CVDs) has become a focal point of scientific debate, with emerging evidence suggesting both beneficial and detrimental roles. This review aims to dissect the multifaceted relationship between BCAAs and cardiovascular health, exploring the molecular mechanisms and clinical implications. Elevated BCAA levels have also been linked to insulin resistance (IR), type 2 diabetes mellitus (T2DM), inflammation, and dyslipidemia, which are well-established risk factors for CVD. Central to these processes are key pathways such as mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-light-chain-enhancer of activate B cells (NF-κB)-mediated inflammation, and oxidative stress. Additionally, the interplay between BCAA metabolism and gut microbiota, particularly the production of metabolites like trimethylamine-N-oxide (TMAO), adds another layer of complexity. Contrarily, some studies propose that BCAAs may have cardioprotective effects under certain conditions, contributing to muscle maintenance and metabolic health. This review critically evaluates the evidence, addressing the biological basis and signal transduction mechanism, and also discusses the potential for BCAAs to act as biomarkers versus active mediators of cardiovascular pathology. By presenting a balanced analysis, this review seeks to clarify the contentious roles of BCAAs in CVD, providing a foundation for future research and therapeutic strategies required because of the rising prevalence, incidence, and total burden of CVDs.
Topics: Humans; Amino Acids, Branched-Chain; Cardiovascular Diseases; Biomarkers; Gastrointestinal Microbiome; Insulin Resistance; Signal Transduction; Diabetes Mellitus, Type 2; Chronic Disease; Inflammation; Oxidative Stress; TOR Serine-Threonine Kinases; Methylamines
PubMed: 38931325
DOI: 10.3390/nu16121972 -
Plants (Basel, Switzerland) Jun 2024Plants utilize the ubiquitin proteasome system (UPS) to orchestrate numerous essential cellular processes, including the rapid responses required to cope with abiotic...
Plants utilize the ubiquitin proteasome system (UPS) to orchestrate numerous essential cellular processes, including the rapid responses required to cope with abiotic and biotic stresses. The 26S proteasome serves as the central catalytic component of the UPS that allows for the proteolytic degradation of ubiquitin-conjugated proteins in a highly specific manner. Despite the increasing number of studies employing cell-free degradation assays to dissect the pathways and target substrates of the UPS, the precise extraction methods of highly potent tissues remain unexplored. Here, we utilize a fluorogenic reporting assay using two extraction methods to survey proteasomal activity in different tissues. This study provides new insights into the enrichment of activity and varied presence of proteasomes in specific plant tissues.
PubMed: 38931128
DOI: 10.3390/plants13121696 -
Microorganisms May 2024(1) Background: The mycophagous mite, , was found to feed on entomopathogenic fungi (EPF) in our previous experiments, which seriously impacted the culture and...
(1) Background: The mycophagous mite, , was found to feed on entomopathogenic fungi (EPF) in our previous experiments, which seriously impacted the culture and preservation of fungal strains. Therefore, it is necessary to investigate the biological characteristics of the occurrence and damage to EPF. (2) Methods: The mite's growth and development and feeding preference were surveyed by comparative culture and observation; also, optical and electronic microscopies were employed. (3) Results: could survive normally after being fed on seven EPF species, including , , , , , , and . The first four fungi were the mite's favorites with their greater feeding amount and shorter developmental duration. Interestingly, the mite could also feed on and , but this led to the mite's death. After feeding on and , the mites began to die after 24 h, and the mortality rate reached 100% by 72 h. Observation under optical microscopy and scanning electron microscopy revealed that the conidia of and adhered to the mite's surface, but there was no evidence of penetration or invasion. However, dissection observation indicated that the two species germinate and grow within the mite's digestive tract, which implies that generalists with broad-spectrum hosts and the production of destruxins have acaricidal activity toward the mycophagous mites.
PubMed: 38930424
DOI: 10.3390/microorganisms12061042